Evidence map›Paper›PMID 25955828›Full record

ArticlePLoS pathogens2015

The NLRP3 Inflammasome Is a Pathogen Sensor for Invasive Entamoeba histolytica via Activation of α5β1 Integrin at the Macrophage-Amebae Intercellular Junction.

Leanne Mortimer, France Moreau, Steve Cornick, Kris Chadee

Open access · goldAbstract read
In one paragraph

Article in PLoS pathogens, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.

0numbers the graph read from it
0cells of the map it votes in
56citing papers in PubMed
6.6field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

56 citing papers in PubMed, 79 citations in OpenAlex.

  1. Article
  2. ACPA-Induced ATP release and KCell communication and signaling : CCS · 2025
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  9. Gasdermins in Innate Host Defense AgainstFrontiers in immunology · 2022
    Review
  10. Article
  11. Review
  12. Article
  13. Article
  14. Review
  15. P2RX7 at the Host-Pathogen Interface of Infectious Diseases.Microbiology and molecular biology reviews : MMBR · 2021
    Review
  16. Review
  17. Article
  18. The NF-κB Pathway: Modulation byFrontiers in cellular and infection microbiology · 2021
    Review
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 1 institution in 1 country.

Leanne MortimerDepartment of Microbiology, Immunology and Infectious Diseases, Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada.
France MoreauDepartment of Microbiology, Immunology and Infectious Diseases, Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada.
Steve CornickDepartment of Microbiology, Immunology and Infectious Diseases, Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada.
Kris ChadeeDepartment of Microbiology, Immunology and Infectious Diseases, Snyder Institute for Chronic Diseases, University of Calgary, Calgary, Alberta, Canada.
University of Calgary · CA

Funding

Canadian Institutes of Health Research 12249
6 · The paper itself

Abstract

Entamoeba histolytica (Eh) is an extracellular protozoan parasite of humans that invades the colon to cause life-threatening intestinal and extra-intestinal amebiasis. Colonized Eh is asymptomatic, however, when trophozoites adhere to host cells there is a considerable inflammatory response that is critical in the pathogenesis of amebiasis. The host and/or parasite factors that trigger the inflammatory response to invading Eh are not well understood. We recently identified that Eh adherence to macrophages induces inflammasome activation and in the present study we sought to determine the molecular events upon contact that coordinates this response. Here we report that Eh contact-dependent activation of α5β1 integrin is critical for activation of the NLRP3 inflammasome. Eh-macrophage contact triggered recruitment of α5β1 integrin and NLRP3 into the intercellular junction, where α5β1 integrin underwent activation by an integrin-binding cysteine protease on the parasite surface, termed EhCP5. As a result of its activation, α5β1 integrin induced ATP release into the extracellular space through opening of pannexin-1 channels that signalled through P2X7 receptors to deliver a critical co-stimulatory signal that activated the NLRP3 inflammasome. Both the cysteine protease activity and integrin-binding domain of EhCP5 were required to trigger α5β1 integrin that led to ATP release and NLRP3 inflammasome activation. These findings reveal engagement of α5β1 integrin across the parasite-host junction is a key regulatory step that initiates robust inflammatory responses to Eh. We propose that α5β1 integrin distinguishes Eh direct contact and functions with NLRP3 as pathogenicity sensor for invasive Eh infection.

Indexed as

Host-Pathogen InteractionsAnimalsCarrier ProteinsCell AdhesionCells, CulturedCysteine ProteasesEntamoeba histolyticaEntamoebiasisHumansImmunity, InnateInflammasomesIntegrin alpha5beta1MacrophagesMice, Inbred C57BLMice, KnockoutMutationCarrier ProteinsCysteine ProteasesInflammasomesIntegrin alpha5beta1NLR Family, Pyrin Domain-Containing 3 ProteinNLRP3 protein, humanNlrp3 protein, mouseProtozoan ProteinsRecombinant Proteins

Identifiers

PMID25955828
PMCPMC4425650
OpenAlexW1518556167

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.